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A Cure for the Flu?

WASHINGTON, D.C.--There may be a magic bullet after all. Scientists at a small California biotech company announced at a press conference here today that they have developed a drug that cures the flu by halting the spread of influenza virus between cells in the mucous membranes of the nose and lungs.

So far, the drug has been tested only in animals. If it succeeds in clinical trials set to begin this spring, it could have a huge impact: Some 20,000 Americans die each year from the flu, and the illness costs as much as $12 billion a year in health care and lost productivity. The new compound "is very exciting," says Robert Sidwell, a virologist with Utah State University in Logan, because unlike current flu vaccines, it seems to stop all influenza strains dead in their tracks.

The new compound, developed by scientists at Gilead Sciences in Foster City, California, blocks the activity of a key viral enzyme, known as neurominidase. The enzyme unleashes newly formed viral particles from cells in which they are produced, enabling the virus to infect other cells. Animal and test tube studies reported in tomorrow's issue of the Journal of the American Chemical Society show that the new compound puts the kibosh on all influenza strains. That success stems from the fact that neurominidase's active region "is almost identical for all the strains of the virus," says Gilead medicinal chemist Choung Kim. The drug also quickly eliminated flu symptoms, such as fever and coughing, in ferrets, the best animal model of the illness. The compound, provisionally christened GS 4104, so far does not appear to cause side effects, says Kim.

Gilead's drug is actually the second of its kind. The first neurominidase blocker was developed by researchers in Australia and the United Kingdom in 1993 and is now in clinical trials run by the British pharmaceutical giant Glaxo Wellcome. The two compounds have a similar chemical structure--both are small, sugarlike molecules--and the same mode of action, says Kim. The Glaxo compound cannot be absorbed by the gut, so it must be given as a nasal spray, nose drops, or via an inhaler.

In contrast, the Gilead compound has an additional lipophilic, or fat-loving, chemical group that allows it to easily cross the fatty membranes of intestinal cells and thus pass into the bloodstream. "That suggests this drug may be stable for oral delivery" as a pill, says Catherine Laughlin, who heads the virology branch of the National Institute of Allergy and Infectious Diseases' division of microbiology and infectious diseases in Bethesda, Maryland. Gilead plans to begin clinical trials this spring with help from the pharmaceutical company Hoffmann-La Roche.